The purpose of this project is develop a better understanding of ribozyme- substrate interactions in vivo and how substrate secondary structure influences the interactions. Methods to predict and determine RNA structure both in vitro and in vivo will be compared, establishing the effect of such structure on ribozyme kinetics. The relation between in vitro and in vivo RNA structures will be evaluated, and ribozymes that target accessible sites based on the in vivo structural analyses will be tested for their ability to inhibit HIV-1 in cell culture.